NCT07294495

Effect of Henagliflozin on Myocardial Fibrosis in Non-Obstructive HCM: A Randomized, Double-Blind, Placebo-Controlled Trial Using 68Ga/18F-FAPI PET/CMR

A Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Effect of Henagliflozin on Myocardial Fibrosis Burden in Patients With Non-Obstructive Hypertrophic Cardiomyopathy Using 68Ga/18F-FAPI PET/CMR

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 150 (estimated)
• Sponsor: Shanghai East Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

his is a single-center, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the effect of Henagliflozin (an SGLT2 inhibitor) on myocardial fibrosis burden in patients with non-obstructive hypertrophic cardiomyopathy (nHCM). The study will use 68 68 Ga/ 18 18 F-FAPI PET/CMR imaging to quantitatively assess changes in active fibroblast activity after 6 months of treatment. A total of 150 eligible adult patients with nHCM (FAPI-positive at baseline, NYHA class I-III) will be enrolled and randomized in a 1:1 ratio to either the Henagliflozin group (10 mg once daily) or the placebo group for a 6-month treatment period. The primary endpoint is the change in myocardial FAPI target-to-background ratio (ΔTBR) at 6 months. Secondary endpoints include changes in FAPI SUVmax, FAPI burden percentage (FAV%), cardiac structure and function parameters, 6-minute walk distance, NYHA classification, NT-proBNP levels, and quality-of-life scores. Exploratory analyses will assess clinical events over 12 months, such as heart failure hospitalization, atrial fibrillation, ventricular arrhythmias, and cardiovascular death. The study employs stratified block randomization based on baseline FAPI burden, central randomization and blinding via IWRS, independent core laboratory imaging evaluation, and an intention-to-treat analytical approach. It aims to provide early evidence for the anti-fibrotic effect of Henagliflozin in nHCM and to validate FAPI-PET/CMR as an imaging biomarker for fibrosis activity.

Detailed description

This is a single-center, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the effect of Henagliflozin, an SGLT2 inhibitor, on myocardial fibrosis burden in patients with non-obstructive hypertrophic cardiomyopathy. The study will utilize integrated Gallium-68 or Fluorine-18 labeled FAPI PET/CMR imaging to quantitatively assess changes in active fibroblast activity following six months of treatment. A total of 150 eligible adult patients with non-obstructive hypertrophic cardiomyopathy, who are FAPI-positive at baseline and classified as NYHA functional class I to III, will be enrolled. Participants will be randomized in a one-to-one ratio to receive either Henagliflozin 10 mg once daily or a matching placebo for a treatment period of six months. The primary endpoint of the study is the change in myocardial FAPI target-to-background ratio from baseline to six months. Secondary endpoints include changes in other FAPI parameters such as SUVmax and FAPI-active volume percentage, as well as changes in cardiac structure and function parameters assessed by CMR, six-minute walk distance, NYHA functional class, NT-proBNP levels, and quality of life scores. Furthermore, exploratory analyses will assess clinical events over a 12-month period, including heart failure hospitalization, atrial fibrillation, ventricular arrhythmias, and cardiovascular death. The trial employs a stratified block randomization method based on baseline FAPI burden, with central randomization and blinding maintained through an interactive web response system. All imaging data will be evaluated by an independent core laboratory to ensure objectivity, and statistical analyses will adhere to the intention-to-treat principle. This study aims to generate early evidence regarding the potential anti-fibrotic effect of Henagliflozin in non-obstructive hypertrophic cardiomyopathy and to validate FAPI-PET/CMR as a promising imaging biomarker for monitoring myocardial fibrosis activity.

Conditions

• HCM - Hypertrophic Cardiomyopathy

Interventions

Type	Name	Description
DRUG	Henagliflozin (SGLT2 Inhibitor)	This intervention involves the oral administration of Henagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, at a dose of 10 mg once daily for a period of 6 months. Henagliflozin is provided as a film-coated tablet identical in appearance to the matched placebo used in the control arm. The intervention is administered in a double-blind manner as an add-on to stable standard background therapy for non-obstructive hypertrophic cardiomyopathy. This study specifically investigates the potential anti-fibrotic effects of Henagliflozin on active myocardial fibrosis, as quantified by novel FAPI PET/CMR imaging, in a patient population without diabetes mellitus.
DRUG	Placebo	This intervention involves the oral administration of a matched placebo tablet once daily for a period of 6 months. The placebo is manufactured to be identical in appearance (size, shape, color, coating), packaging, and administration schedule to the active comparator, Henagliflozin 10 mg tablet. It contains no active pharmaceutical ingredient. The intervention is administered in a double-blind manner as an add-on to stable standard background therapy for non-obstructive hypertrophic cardiomyopathy, serving as the control to isolate and evaluate the specific pharmacological effects of the SGLT2 inhibitor.

Timeline

• Start date: 2026-01-07
• Primary completion: 2028-12-31
• Completion: 2028-12-31
• First posted: 2025-12-19
• Last updated: 2025-12-19

Locations

1 site across 1 country: China